We wish to continue our studies which are designed to: a) identify the most useful circadian schedules for the administration of antimetabolites in experimental and clinical cancer chemotherapy. These studies will be carried out in animals pretreated or not with either dexamethasone (DEX), isoproterenol (ISO) or a combination of both. Specifically we want to verify whether the phase shifts which these drugs produce in the circadian mitotic rhythm result in extended circadian periods of minimum sensitivity (low toxicity) to chemotherapeutic agents. b) Identify basic differences in the circadian distribution of mitoses of normal and neoplastic cells, primarily in terms of circadian phase shifts which have been determined to occur in normal tissues in response to dexamethasone and isoproterenol. For these purposes, chemotherapy will be carried out in normal and tumor bearing mice and rats in which the circadian mitotic rhythm will be identified with the aid of biochemical and histological techniques, 3H Thymidine incorporation into DNA and mitotic index determinations.